ABSTRACT: Core D Neuropathology Alzheimer's disease (AD) is a multifactorial and complex disease and includes the impact of the cerebrovascular system on the induction and progression of the dementia. Correlation of experimental findings in disease models with the changes in the human CNS can now be approached with cellular, molecular and genetically related molecular markers. System connectivity is now approached three-dimensionally using novel methods of cellular labeling of animal model or human tissues combined with imaging, as seen with CLARITY-based preparations viewed with two-photon or lightsheet imaging. In AIM 1 the Neuropathology Core serves these functions by providing at autopsy, CNS tissues for accurate diagnoses of AD and accompanying pathologies. AIM 2 provides individual and multiple investigators with diseased tissues, blood, blood products and CSF for research. Contribution to a common database in AIM 3 serves to correlate neurological, psychometric, neuroimaging and behavioral data with the neuropathological and molecular findings. It also coordinates contribution of tissues, blood and cerebrospinal fluid (CSF) to national initiatives that also define genomic data, such as ApoE and other risk factors, and biomarker information addressed in AIMS 4-6, that highlight those functional in the neurovascular unit and in the blood-brain-barrier, and the recently described ?glymph? system. In AIM 7, training and education of neuropathologists, neurologists, and neuroscientists bring AD and related dementia further into focus by defining the potential translational approaches leading to novel therapies.